Menstrual Blood-Derived Endometrial Stem Cells Ameliorate Ovarian Senescence by Relieving Oxidative Stress-Induced Inflammation.

Abstract

Senescence is a degenerative process that occurs with ageing, and in the female reproductive system, senescence occurs earlier in the ovaries than in other tissues and organs, which implies a decrease in oocyte quality and exhaustion of the primordial follicular pool, leading to impaired ovarian function and an inability to maintain normal fertility. Unfortunately, the development of curative and effective treatments for ovarian senescence is still a considerable challenge. Currently, mesenchymal stem cells (MSCs)-based therapies for treating various refractory diseases, especially ovarian dysfunction, have been extensively studied and confirmed. However, the mechanisms by which MSCs improve ovarian senescence are not yet clear. Therefore, in this study, a mouse ageing model was generated via the intraperitoneal injection of a D-galactose (D-gal) solution, and the effects of menstrual blood-derived endometrial stem cells (MenSCs) transplantation on the ovarian follicle count, fibrosis level, and degree of apoptosis were evaluated. Subsequently, an ovarian granulosa cell ageing model was induced with H₂O₂, and CCK-8 assays, flow cytometry, mitochondrial membrane potential analysis and Western blotting were subsequently performed to further investigate the potential mechanism by which MenSCs ameliorate cellular oxidative damage. Overall, our findings demonstrated that MenSCs treatment can increase the cellular antioxidant capacity by activating the NRF2/HO-1 signalling pathway and further ameliorate the inflammatory ovarian microenvironment, apoptosis and dysfunction in ageing mice. These results provide reliable evidence and support for MenSCs-based therapy for ovarian senescence.